Imaging long-lasting deposition

Positron emission tomography (PET) using the radioligand for tau protein flortaucipir is a recently developed noninvasive method for measuring tau protein deposition. Although traumatic brain injury (TBI) has been associated with increased tau in postmortem samples, the long-term effects of a single TBI on tau deposition and its relationship with brain damage is unclear. Now, Gorgoraptis et al. reported increased flortaucipir signal (index of increased tau deposition) in long-term TBI survivors compared to healthy controls. Cerebrospinal fluid biomarkers of neurodegeneration and white matter damage correlated with flortaucipir signal, suggesting that flortaucipir PET imaging might be useful for diagnosis and prognostication of neuronal damage after TBI.

Abstract

Traumatic brain injury (TBI) can trigger progressive neurodegeneration, with tau pathology seen years after a single moderate-severe TBI. Identifying this type of posttraumatic pathology in vivo might help to understand the role of tau pathology in TBI pathophysiology. We used flortaucipir positron emission tomography (PET) to investigate whether tau pathology is present many years after a single TBI in humans. We examined PET data in relation to markers of neurodegeneration in the cerebrospinal fluid (CSF), structural magnetic resonance imaging measures, and cognitive performance. Cerebral flortaucipir binding was variable, with many participants with TBI showing increases in cortical and white matter regions. At the group level, flortaucipir binding was increased in the right occipital cortex in TBI when compared to healthy controls. Flortaucipir binding was associated with increased total tau, phosphorylated tau, and ubiquitin carboxyl-terminal hydrolase L1 CSF concentrations, as well as with reduced fractional anisotropy and white matter tissue density in TBI. Apolipoprotein E (APOE) ε4 genotype affected the relationship between flortaucipir binding and time since injury, CSF β amyloid 1–42 (Aβ42) concentration, white matter tissue density, and longitudinal Mini-Mental State Examination scores in TBI. The results demonstrate that tau PET is a promising approach to investigating progressive neurodegeneration associated with tauopathy after TBI.